rs451360

chr5-1319565-C-Achr5-1319565-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030782.5(CLPTM1L):c.1532+1051G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,252 control chromosomes in the GnomAD database, including 2,193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2193 hom., cov: 33)
• Consequence: CLPTM1L NM_030782.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0780

Genes affected

CLPTM1L (HGNC:24308): (CLPTM1 like) The protein encoded by this gene is a membrane protein whose overexpression in cisplatin-sensitive cells causes apoptosis. Polymorphisms in this gene have been reported to increase susceptibility to several cancers, including lung, pancreatic, and breast cancers. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-1319565-C-A is Benign according to our data. Variant chr5-1319565-C-A is described in ClinVar as [Benign]. Clinvar id is 1226954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLPTM1L	NM_030782.5	c.1532+1051G>T		intron_variant		ENST00000320895.10
CLPTM1L	XM_011514144.3	c.1529+1051G>T		intron_variant
CLPTM1L	XM_024446222.2	c.998+1051G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1L	ENST00000320895.10	c.1532+1051G>T		intron_variant		1	NM_030782.5	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23290 AN: 152134 Hom.: 2191 Cov.: 33

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.159

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23288 AN: 152252 Hom.: 2193 Cov.: 33 AF XY: 0.150 AC XY: 11182 AN XY: 74430

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.0986

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0733 Hom.: 116

Bravo AF: 0.146

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 28, 2020

This variant is associated with the following publications: (PMID: 26716642) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.79
Dann	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs451360; hg19: chr5-1319680; COSMIC: COSV57989826; COSMIC: COSV57989826;